Limb girdle muscular dystrophies

Limb Girdle Muscular Dystrophies (LGMD) include a clinically heterogeneousgroup of disorders, ranging from severe childhood recessive muscular dystrophy to adultonsetdystrophy or asymptomatic patients with high CK.There are at least 25 different forms of LGMD, varying in age of onset, course, anddisability. Dominant forms (LGMD1A-1H) are the less frequent group, whereas recessiveforms (LGMD2A-2Q) account for about 80% of total LGMDs.Dominant forms are usually characterized by mild limb girdle and axial weakness,with onset after 12 years of age; the most frequent cases are caveolinopathies,laminopathies and myotilinopathies. Myopathic and neurogenic features can be found inmuscle biopsy and EMG. Appropriate genetic studies are needed to confirm the clinicaldiagnosis.Among recessive LGMDs, calpainopathy (LGMD2A), sarcoglycanopathies(LGMD2C-2F) and dysferlinopathy (LGM2B) are the most frequent. Sarcoglycanopathiesinclude some of the most severe LGMD forms, characterized by limb girdleweakness with early onset (before 12 years). Classical LGMD present limb girdleweakness after 12 years of age, Gowers sign, difficulty in climbing stairs, myopathicEMG and dystrophic biopsy. Muscle MRI is useful for prognostic or follow-up purposes.A difficult task is molecular diagnosis: muscle biopsies undergo multiple proteintesting (by immunohistochemistry and immunoblotting) to identify muscle specificdefects. Gene mutation analysis are conducted to confirm protein diagnosis, and also tocharacterize those disorders in which no protein markers are available.There is a large group of LGMD cases, mostly sporadic and with mild or atypicalphenotypes (proximo-distal weakness), in which a molecular diagnosis is missing andlinkage analysis is not feasible. It is possible that most of them are caused by mutations innovel candidate genes, whose molecular characterization remains an open challenge forfuture research.